This study examined quality of life and its associated factors in siblings of children with severe motor and intellectual disabilities in Japan. The participants were 789 siblings of children with a disability and their primary caregivers. We used the Kinder Lebensqualität Fragebogen questionnaire to assess the quality of life of siblings. The mean age of the siblings was 12.21 ± 3.07 years, and the mean quality of life score was 69.63 ± 12.55 points, which is higher than that of the general population of children of the same age. It was revealed that the following factors contributed to higher quality of life scores: a closer relationship with the child with a disability, younger age, the primary caregiver's lower care burden, later birth order of siblings (i.e., younger siblings), higher family empowerment, and female gender of siblings. The relationship with the child with a disability had the strongest influence on siblings' quality of life. Our study suggests the need for nursing interventions that focus on the whole family to enhance siblings' quality of life.